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Ull somatic APs. (No C stimulus was provided.) C. a shorter P1 2 interstimulus interval (isi) results in a reduced P2 depolarization,representing the electrotonic potential from an AP that failed in the stem axon before invading the soma. (Again, no C stimulus was provided.) D. a single central stimulus produces a somatic AP. (No P stimuli were provided.) E. the C depolarization is absent due to GW610742MedChemExpress GW610742 collision of the C AP in the central process with the P2 AP, which has successfully transited the T-junction. F, a shorter P1 2 interval produces only an electrotonic P2 potential in the soma, but the C depolarization is still absent, indicating passage of the P2 AP into the central process. G, a still shorter P1 2 interval results in complete failure of P2 somatic depolarization, accompanied by the arrival of an unblocked C AP in the soma. This demonstrates that a somatic electrotonic potential represents an AP transiting the T-junction, while complete failure of somatic depolarization represents AP propagation failure at the T-branch. Findings in three other neurons were the same, including one in which polarities were reversed (paired central stimuli GW0742 site colliding with a late peripheral stimulus).C2012 The Authors. The Journal of PhysiologyC2012 The Physiological SocietyG. Gemes and othersJ Physiol 591.significantly exceeded those recorded in the soma (Fig. 4B; P < 0.0001). Together with the collision data, these findings strongly suggest that the T-junction is the point of failure for both entry into the stem axon and transit to the opposing process.Conduction fails at longer interstimulus intervals in a train than in a pair of pulsesTo identify if repetitive firing in trains can maintain successful conduction at the same inter-pulse intervals as for the initial pair, we compared the maximum followingfrequency for 20 AP trains to the same neuron's maximum instantaneous firing rate (1 per inter-pulse interval) for a pair of APs during the RP protocol. These two measures are correlated (P < 0.001, R2 = 0.52 for all neurons, n = 303), but the maximum frequency is substantially slower for a train of 20 APs compared with a pair of APs (train rate per pair rate of 0.66 ?0.03 for Ao -type fibres, n = 154; 0.62 ?0.03 for Ai -type, n = 128; and 0.18 ?0.04 for C-type, n = 21; P < 0.001 for C-type vs. Ao and Ai ; no effect of injury groups). This reveals that sustained firing progressively generates a condition that impedes successful AP propagation through the T-junction.Figure 4. Influence of neuronal type and injury on impulse propagation A, RP of sensory neurons during paired stimulation. Panels show data according to neuron type and the injury group. Spinal nerve ligation (SNL)4 and SNL5 are neurons from the L4 and L5 ganglions from animals after SNL surgery. The central indicator bars represent the median value. The P-value indicates the probability of a main effect for injury, and significant post hoc comparisons are shown by connecting brackets. P < 0.05, P < 0.001. Note the broken y-axis with two different scales. B, the maximal stimulation rate (the following frequency) that leads to conduction into the stem axon of all APs in a train of 20 APs. P < 0.01.C2012 The Authors. The Journal of PhysiologyC2012 The Physiological SocietyJ Physiol 591.Impulse propagation after sensory neuron injuryMaximal somatic firing rate during conducted trains is regulated at a site other than the somaWe hypothesized that if failed propagation through the T-junctio.Ull somatic APs. (No C stimulus was provided.) C. a shorter P1 2 interstimulus interval (isi) results in a reduced P2 depolarization,representing the electrotonic potential from an AP that failed in the stem axon before invading the soma. (Again, no C stimulus was provided.) D. a single central stimulus produces a somatic AP. (No P stimuli were provided.) E. the C depolarization is absent due to collision of the C AP in the central process with the P2 AP, which has successfully transited the T-junction. F, a shorter P1 2 interval produces only an electrotonic P2 potential in the soma, but the C depolarization is still absent, indicating passage of the P2 AP into the central process. G, a still shorter P1 2 interval results in complete failure of P2 somatic depolarization, accompanied by the arrival of an unblocked C AP in the soma. This demonstrates that a somatic electrotonic potential represents an AP transiting the T-junction, while complete failure of somatic depolarization represents AP propagation failure at the T-branch. Findings in three other neurons were the same, including one in which polarities were reversed (paired central stimuli colliding with a late peripheral stimulus).C2012 The Authors. The Journal of PhysiologyC2012 The Physiological SocietyG. Gemes and othersJ Physiol 591.significantly exceeded those recorded in the soma (Fig. 4B; P < 0.0001). Together with the collision data, these findings strongly suggest that the T-junction is the point of failure for both entry into the stem axon and transit to the opposing process.Conduction fails at longer interstimulus intervals in a train than in a pair of pulsesTo identify if repetitive firing in trains can maintain successful conduction at the same inter-pulse intervals as for the initial pair, we compared the maximum followingfrequency for 20 AP trains to the same neuron's maximum instantaneous firing rate (1 per inter-pulse interval) for a pair of APs during the RP protocol. These two measures are correlated (P < 0.001, R2 = 0.52 for all neurons, n = 303), but the maximum frequency is substantially slower for a train of 20 APs compared with a pair of APs (train rate per pair rate of 0.66 ?0.03 for Ao -type fibres, n = 154; 0.62 ?0.03 for Ai -type, n = 128; and 0.18 ?0.04 for C-type, n = 21; P < 0.001 for C-type vs. Ao and Ai ; no effect of injury groups). This reveals that sustained firing progressively generates a condition that impedes successful AP propagation through the T-junction.Figure 4. Influence of neuronal type and injury on impulse propagation A, RP of sensory neurons during paired stimulation. Panels show data according to neuron type and the injury group. Spinal nerve ligation (SNL)4 and SNL5 are neurons from the L4 and L5 ganglions from animals after SNL surgery. The central indicator bars represent the median value. The P-value indicates the probability of a main effect for injury, and significant post hoc comparisons are shown by connecting brackets. P < 0.05, P < 0.001. Note the broken y-axis with two different scales. B, the maximal stimulation rate (the following frequency) that leads to conduction into the stem axon of all APs in a train of 20 APs. P < 0.01.C2012 The Authors. The Journal of PhysiologyC2012 The Physiological SocietyJ Physiol 591.Impulse propagation after sensory neuron injuryMaximal somatic firing rate during conducted trains is regulated at a site other than the somaWe hypothesized that if failed propagation through the T-junctio.

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